GM mossies show promise

GENETICALLY modified mosquitoes could prove effective in tackling dengue fever and other insect-borne diseases, a UK-based scientific team report has shown.
The male mosquitoes are modified so their offspring die before reproducing. Reports of the study was published in the October issue of Nature Biotechnology journal.
In a dengue-affected part of the Cayman Islands in Africa, researchers found the GM males mated successfully with wild females.
They said such mating had not before been proven in the wild, and could cut the number of disease-carrying mosquitoes.
Dengue, currently plaguing the Marshall Islands, north of Papua New Guinea, is caused by a virus transmitted by the Aedes aegypti mosquito as it bites.
The World Health Organisation (WHO) estimates that there may be 50 million cases each year, and the incidence is rising, with some countries reporting what the WHO terms “explosive” outbreaks.
As yet, there is no vaccine, the BBC reported, adding that as far back as the 1940s, it was realised that releasing sterile males into the wild could control insects that carried disease or were agricultural pests.
When females breed with the sterile males rather than wild fertile ones, there will be no viable offspring, meaning there are fewer mosquitoes around to transmit the disease.
In the 1950s, the screwworm fly was eradicated from the Caribbean island of Curacao using males sterilised by radiation.
But the technology has not worked so well with disease-carrying insects.
Generally, the sterilising process weakens the males so much that they struggle to mate; the wild males are dominant.
Oxitec, a company spun off from Oxford University, uses a genetic engineering approach.
Offspring of their GM males live through the larval stage but die as pupae, before reaching adulthood.
In the latest study, the research group – which includes scientists from Imperial College London and the Liverpool School of Tropical Medicine – released batches of GM mosquitoes in 2009 in an area of the Cayman Islands where Aedes aegypti are common, and dengue sometimes present.
A proportion of the eggs collected from the study area in subsequent weeks carried the introduced gene, meaning the biotech mosquitoes had mated successfully.
The GM males made up 16% of males in the study area, and fathered 10% of the larvae; so they were not quite as successful as the wild males, but not significantly worse.
“We were really surprised how well they did,” Luke Alphey, Oxitec’s chief scientific officer and a visiting professor at Oxford University told BBC.
“For this method, you just need to get a reasonable proportion of the females to mate with GM males – you will never get the males as competitive as the wild ones, but they do not have to be, they just have to be reasonably good.
“This study is the first to show that the mosquito population could be suppressed this way,” Dr Raman Velayudhan, a WHO dengue expert, said.
“The fitness level is much better (compared with previous attempts) – it is almost the same as in wild mosquitoes,” he told the BBC.
Cognisant that genetic engineering is a technology that carries the potential for risks as well as benefits, the WHO is finalising guidance on how GM insects should be deployed in developing countries such as PNG.
The field seems to be hotting up, with other research groups recently creating Anopheles mosquitoes that are immune to the malaria parasite they normally carry, and making male Anopheles that lack sperm.
Malaria is a prime target for these approaches simply because it is such an important disease; but arguably it is more needed in diseases such as dengue where there are few alternatives.
“For malaria, there are effective alternatives like bednets, but they won’t work for dengue because the mosquitoes bite during daytime,” said Dr Alphey.
“We do not advocate (GM mosquitoes) as a ‘magic bullet’ that will solve all dengue in one go, so the question is how it fits in as part of an integrated programme – and for dengue, it would be a huge component of an integrated programme.”
Funding for the Oxitec approach has come from a number of sources including private investors, charities, Oxford University and governments, and the Cayman Islands authorities were willing to take part in the field trial.
The genetic approach used to create the mosquitoes is a system known as tetracycline-controlled transcriptional activation (tTA).
The tTA gene is spliced into the insect’s genome in such a way that the protein it makes increases the gene’s activity – a positive feedback loop.
The cells make more and more tTA protein – and in doing so, have little capacity for making any other proteins. Eventually, this kills the insects.
When the male larvae are reared at Oxitec, this process is turned off by keeping them in water containing the antibiotic tetracycline, which inhibits the feedback process.
When the males breed in the wild, however, tTA genes in their offspring are fully active.
In principle, a process that allows larvae to hatch and stay alive for many days should be more advantageous than the traditional approach of producing infertile eggs, as the larvae will consume food that could otherwise be used by viable larvae from the union of wild males and females.
The next step in the work is to demonstrate that deploying GM males does suppress the insect population enough that it is likely to have an impact on dengue incidence.
Dr Alphey told BBC results from a project last year in the Cayman Islands suggested this had been achieved.
But, according to Daily News, critics say the process is by no means foolproof.
The newspaper quoted Alfred Handler, a geneticist at the Agriculture Department in Gainesville, Florida, as saying  the mosquitoes can evolve resistance to the lethal gene while being bred for generations in a lab.
Todd Shelly, an entomologist for the Agriculture Department in Hawaii, also said in a commentary published on Sunday by Nature Biotechnology that 3.5% of the insects in a lab test survived to adulthood despite presumably carrying the lethal gene.
Also, the sorting of male and female mosquitoes, which is done by hand, can result in up to 0.5% of the released insects being female, the commentary said.
If millions of mosquitoes were released, even that small percentage of females could lead to a temporary increase in disease spread, it was reported by the New York Times.
Oxitec and a molecular biologist, Anthony A. James of the University of California, Irvine, say they have developed a solution – a genetic modification that makes female mosquitoes, but not males, unable to fly.
The grounded females cannot mate or bite people, and separating males from females before release would be easier.
The World Health Organisation expects to release guidance on how GM insects should be deployed in developing countries by the end of the year. – BBC